Spermine Inhibition of Monocyte Activation and Inflammation

Zhang, Minghuang; Borovikova, Lyudmila V.; Wang, Haichao; Metz, Christine; Tracey, Kevin J.

doi:10.1007/bf03402072

Cited by 80 publications

(50 citation statements)

References 31 publications

(45 reference statements)

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“…[18][19][20][21] The finding that N. procerum LAE dose-dependently inhibits LPS-induced neutrophil accumulation in the mouse pleural cavity, reinforces our previous results 1) and clearly demonstrates the anti-inflammatory activity of this extract. The multistep process underlying the mechanisms involved in the development of endotoxin triggered tissue neutrophilia depends on at least three combined cellular components: (i) resident cells that primarily recognize the LPS; (ii) the chemoattractants/cytokines produced in situ (e.g., PAF, MIP-1a and KC); and (iii) the transmigrating and activated neutrophils themselves.…”

Section: Discussionsupporting

confidence: 82%

Anti-inflammatory Activity in the Aqueous Crude Extract of the Leaves of Nidularium procerum: A Bromeliaceae from the Brazilian Coastal Rain Forest

Amendoeira¹,

Frutuoso²,

Zanon³

et al. 2005

Biological & Pharmaceutical Bulletin

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Brazilian flora, especially in the Brazilian coastal rain forest, remains poorly studied regarding its chemical and pharmacological potential. A recent study published by our group indicates that Nidularium procerum, the most common representative of the bromeliaceae family, has potent analgesic and anti-inflammatory activities.1) Bromeliaceae, one of the largest botanical families of the New World, is extensively distributed in tropical America.2) This family comprises 46 genera encompassing about 2500 species from which 20 genera and 245 species are found in the State of Rio de Janeiro. The Brazilian coastal rain forest is the preferred habitat of Bromeliaceae (81.8%) where the greatest genetic diversity and the highest degree of endemism is found.3) Species of Nidularium are well spread in the coastal rain forest from Bahia State, in the northeast region of Brazil, to Rio Grande do Sul State in the south. 4)Our previous results indicate that N. procerum extracts have strong analgesic activity, which is not associated with the activation of opioid receptors, but is mechanistically due to a selective inhibition of PGE 2 production.1) In addition, we showed that the aqueous extract of N. procerum leaves (LAE) inhibited LPS-induced neutrophil accumulation in the mouse pleural cavity, but the molecular mechanism for this anti-inflammatory effect was not investigated.1) Here, we investigated the mechanisms involved in the anti-inflammatory effects of N. procerum aqueous extract on the LPS-induced pleurisy model. We showed that in addition to LPS-induced neutrophil influx, N. procerum also inhibited LPS-driven in vivo neutrophil activation (as attested by inhibition of lipid body formation) and PAF-and fMLP-induced pleural neutrophilia. The mechanisms involved in N. procerum-mediated inhibition of neutrophil recruitment appear to involve decreased production of key inflammatory mediators of LPSdriven response, such as PGE 2 and inflammatory cytokines (IL-1 and IL-6), and an impaired locomotory activity of migrating neutrophils. MATERIALS AND METHODS Plant MaterialNidularium procerum LINDMAN was collected at the National Biological Reserve of Poço das Antas, Silva Jardim, Rio de Janeiro State, Brazil. Identification of the botanical material was made by Dr. Tânia Wendt and Dr. Elton Leme and a voucher has been deposited at the Herbarium of the Rio de Janeiro Botanical Garden, under the number 304732.Preparation of Plant Extracts The aqueous extract of leaves (LAE) (22 g) was obtained by infusing dried leaves (500 g) into 2.5 l of boiling distilled water until the water cooled down to room temperature, followed by filtration and lyophilization as previously described. 1)Animals Male Swiss mice (obtained from the Oswaldo Cruz Foundation breeding unit) weighing 20-30 g, were used. The animals were maintained with free access to food and water and kept at 25-28°C with controlled 12 h light/dark cycle at the Department of Physiology and Pharmacodynamics. The experiments in this study received prior approval from the Oswal...

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Section: Discussionsupporting

confidence: 82%

Anti-inflammatory Activity in the Aqueous Crude Extract of the Leaves of Nidularium procerum: A Bromeliaceae from the Brazilian Coastal Rain Forest

Amendoeira¹,

Frutuoso²,

Zanon³

et al. 2005

Biological & Pharmaceutical Bulletin

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“…Furthermore, local application of spermine inhibited the development of acute footpad inflammation induced by carrageenin (35). The administration of an inhibitor of polyamine transport system worsened the inflammation (36), indicating that spermine released from injured cells is taken up actively by cells of the immune system (37). The inhibition of the counterregulatory mechanisms by spermine depletion by acute overexpression of the rate-limiting catabolic enzyme SSAT might contribute to the observed necrosis.…”

Section: Discussionmentioning

confidence: 99%

Activation of polyamine catabolism in transgenic rats induces acute pancreatitis

Alhonen

Parkkinen²,

Keinänen³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Polyamines are required for optimal growth and function of cells. Regulation of their cellular homeostasis is therefore tightly controlled. The key regulatory enzyme for polyamine catabolism is the spermidine͞spermine N 1 -acetyltransferase (SSAT). Depletion of cellular polyamines has been associated with inhibition of growth and programmed cell death. To investigate the physiological function SSAT, we generated a transgenic rat line overexpressing the SSAT gene under the control of the inducible mouse metallothionein I promoter. Administration of zinc resulted in a marked induction of pancreatic SSAT, overaccumulation of putrescine, and appearance of N 1 -acetylspermidine with extensive depletion of spermidine and spermine in transgenic animals. The activation of pancreatic polyamine catabolism resulted in acute pancreatitis. In nontransgenic animals, an equal dose of zinc did not affect pancreatic polyamine pools, nor did it induce pancreatitis. Acetylated polyamines, products of the SSAT-catalyzed reaction, are metabolized further by the polyamine oxidase (PAO) generating hydrogen peroxide, which might cause or contribute to the pancreatic inflammatory process. Administration of specific PAO inhibitor, MDL72527 [N 1 ,N 2 -bis(2,3-butadienyl)-1,4-butanediamine], however, did not affect the histological score of the pancreatitis. Induction of SSAT by the polyamine analogue N 1 ,N 11 -diethylnorspermine reduced pancreatic polyamines levels only moderately and without signs of organ inflammation. In contrast, the combination of N 1 ,N 11 -diethylnorspermine with MDL72527 dramatically activated SSAT, causing profound depletion of pancreatic polyamines and acute pancreatitis. These results demonstrate that acute induction of SSAT leads to pancreatic inflammation, suggesting that sufficient pools of higher polyamine levels are essential to maintain pancreatic integrity. This inflammatory process is independent of the production of hydrogen peroxide by PAO.I ntracellular polyamine levels are tightly maintained by a number of mechanisms, suggesting their importance for cell function. This polyamine homeostasis is controlled by their biosynthesis, interconversion, catabolism, secretion, and uptake. Polyamine biosynthesis is regulated by the activities of ornithine and S-adenosylmethionine decarboxylases. Overexpression of ornithine decarboxylase in transgenic rodents affected spermatogenesis (1, 2), rendered animals more resistant to chemically or electrically induced seizure activity (3) and to ischemic insults (4), and enhanced skin papilloma formation (5). However, the activation of polyamine biosynthesis caused by overexpression of ornithine decarboxylase did not result in enhanced accumulation of the higher polyamines spermidine and spermine. Polyamine catabolism is controlled by the activity of spermidine͞spermine N 1 -acetyltransferase (SSAT; refs. 6 and 7). The acetylated products are oxidized further by the polyamine oxidase (PAO) to spermidine and putrescine. We recently generated transgenic mouse lines with ...

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“…To date, numerous studies have investigated the biochemistry and physiology of these biogenic polyamines. As a result, it is well known that biogenic polyamines regulate gene expression at the level of transcription and translation (Wallance et al, 2003;Kusano et al, 2008), have anti-inflammatory effects (Soda et al, 2005) via several mechanisms, exemplified by modulating proinflammatory cytokines such as tumor necrosis factor (Zhang et al, 1999), and play important roles in regulating ion channels (Pegg, 2009). These discoveries suggest that the homeostasis of biogenic polyamines is essential to mammalian life.…”

Section: Introductionmentioning

confidence: 99%

Contribution of a Fermentation Process using <i>Bacillus subtilis</i> (natto) to High Polyamine Contents of Natto, a Traditional Japanese Fermented Soy Food

Kobayashi

Shimojo

Watanabe

2016

FSTR

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We developed a more convenient method for assaying polyamines and re-examined the variation of polyamine contents during each step of the natto production process. The steaming process slightly decreased spermidine in soybeans, and the subsequent fermentation process resulted in 41.1% increase of spermidine and 19.4% reduction of spermine compared with those of steamed soybeans. These results indicated that Bacillus subtilis (natto) produces spermidine during the fermentation process. Further, we determined that spermidine production differs among inoculum strains. It was also suggested that the selection of starter cultures with high spermidine productivity improves polyamine levels in natto.

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Spermine Inhibition of Monocyte Activation and Inflammation

Cited by 80 publications

References 31 publications

Anti-inflammatory Activity in the Aqueous Crude Extract of the Leaves of Nidularium procerum: A Bromeliaceae from the Brazilian Coastal Rain Forest

Anti-inflammatory Activity in the Aqueous Crude Extract of the Leaves of Nidularium procerum: A Bromeliaceae from the Brazilian Coastal Rain Forest

Activation of polyamine catabolism in transgenic rats induces acute pancreatitis

Contribution of a Fermentation Process using <i>Bacillus subtilis</i> (natto) to High Polyamine Contents of Natto, a Traditional Japanese Fermented Soy Food

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